The CSF-Contacting Nucleus Receives Anatomical Inputs From the Cerebral Cortex: A Combination of Retrograde Tracing and 3D Reconstruction Study in Rat

Abstract

ObjectiveThis study aimed to investigate the direct monosynaptic projections from cortical functional regions to the cerebrospinal fluid (CSF)-contacting nucleus for understanding the functions of the CSF-contacting nucleus.MethodsThe Sprague–Dawley rats received cholera toxin B subunit (CB) injections into the CSF-contacting nucleus. After 7–10 days of survival time, the rats were perfused, and the whole brain and spinal cord were sliced under a freezing microtome at 40 μm. All sections were treated with the CB immunofluorescence reaction. The retrogradely labeled neurons in different cortical areas were revealed under a confocal microscope. The distribution features were further illustrated under 3D reconstruction.ResultsThe retrogradely labeled neurons were identified in the olfactory, orbital, cingulate, insula, retrosplenial, somatosensory, motor, visual, auditory, association, rhinal, and parietal cortical areas. A total of 12 functional areas and 34 functional subregions showed projections to the CSF-contacting nucleus in different cell intensities.ConclusionAccording to the connectivity patterns, we conclude that the CSF-contacting nucleus participates in cognition, emotion, pain, visceral activity, etc. The present study firstly reveals the cerebral cortex→CSF-contacting nucleus connections, which implies the multiple functions of this special nucleus in neural and body fluid regulations.

Spatial and single-cell transcriptomics onSSPOPTV mutant mice reveals SCO-spondin’s function in mood regulation through brain barriers

“…DEGs of the spatial clusters “choroid plexus (chpl)”, “cortical subplate + olfactory area (CTXsp + OLF)” and “hypothalamus (HY)” are enriched with the candidate gene sets for stress response and three affective disorders respectively, while DEGs of the cluster “SCO + ventricles (SCO + V)” are enriched with candidate gene sets for stress response and bipolar disorder. Interestingly, the SCO, ventricles and choroid plexus have direct contact with CSF, while the hypothalamus and olfactory area have CSF-contacting neurons 60,61 . CSF-contacting neurons serve as chemoreceptors and mechanosensors for sensing the chemical and mechanical changes in the CSF 62 .…”

“…5c-d ). Of these CSF-contacting regions, the SCO, ventricles and choroid plexus have direct contact with CSF through ependymal cells, while olfactory area and hypothalamus are known to have CSF-contacting neurons 60,61 , suggesting that the deficit of SCO-spondin caused by the PTV mutation may be involved in the abnormal mood-related behaviors. Furthermore, the DEGs of cell types EpenCs, ECs, OLs and MCs are enriched with the above candidate gene sets, respectively ( Fig.…”

“…Interestingly, the SCO, ventricles and choroid plexus have direct contact with CSF, while the hypothalamus and olfactory area have CSF-contacting neurons 60,61 . CSFcontacting neurons serve as chemoreceptors and mechanosensors for sensing the chemical and mechanical changes in the CSF 62 .…”

Can a basic solution activate the inflammatory reflex? A review of potential mechanisms, opportunities, and challenges

“…The somata of these neurons are located in the CSF-contacting nucleus within the brain parenchyma, a structure that has been reported in rodents [111,112) and primates {Song, 2020 #211]. Neurons in the CSF-contacting nucleus send widespread projections to areas involved in visceral activity [100], some of which could potentially modulate the splenic IR and potentially induce an anti-inflammatory shift in the CNS itself.…”

“…3), and/or 2) the choroid plexus, where it can be transported into the cerebrospinal fluid (CSF) by ependymal cells [97,98]. An alkaline shift in the CSF has been shown to stimulate CSF-contacting neurons in the brain parenchyma [99], whose axons target multiple areas across the brain, some of which might be IR-related [100]. Figure created by Ilse Anton (@science_illustrated_by_ilse) as drinking water in comparison with controls given a 0.1-M NaCl solution.…”